Garro Martinez Juan C, Vega-Hissi Esteban G, Andrada Matías F, Duchowicz Pablo R, Torrens Francisco, Estrada Mario R
Area de Quimica Fisica, Facultad de Quimica, Bioquimica y Farmacia, Universidad Nacional de San Luis, Chacabuco 917, San Luis, 5700, Argentina.
Curr Comput Aided Drug Des. 2014;10(2):160-7. doi: 10.2174/1573409910666140410123706.
Lacosamide is an anticonvulsant drug which presents carbonic anhydrase inhibition. In this paper, we analyzed the apparent relationship between both activities performing a molecular modeling, docking and QSAR studies on 18 lacosamide derivatives with known anticonvulsant activity. Docking results suggested the zinc-binding site of carbonic anhydrase is a possible target of lacosamide and lacosamide derivatives making favorable Van der Waals interactions with Asn67, Gln92, Phe131 and Thr200. The mathematical models revealed a poor relationship between the anticonvulsant activity and molecular descriptors obtained from DFT and docking calculations. However, a QSAR model was developed using Dragon software descriptors. The statistic parameters of the model are: correlation coefficient, R=0.957 and standard deviation, S=0.162. Our results provide new valuable information regarding the relationship between both activities and contribute important insights into the essential molecular requirements for the anticonvulsant activity.
拉科酰胺是一种具有碳酸酐酶抑制作用的抗惊厥药物。在本文中，我们通过对18种具有已知抗惊厥活性的拉科酰胺衍生物进行分子建模、对接和定量构效关系（QSAR）研究，分析了这两种活性之间的表观关系。对接结果表明，碳酸酐酶的锌结合位点可能是拉科酰胺和拉科酰胺衍生物的作用靶点，它们与天冬酰胺67、谷氨酰胺92、苯丙氨酸131和苏氨酸200形成了有利的范德华相互作用。数学模型显示，抗惊厥活性与从密度泛函理论（DFT）和对接计算获得的分子描述符之间的关系较差。然而，使用Dragon软件描述符开发了一个QSAR模型。该模型的统计参数为：相关系数R = 0.957，标准差S = 0.162。我们的结果提供了关于这两种活性之间关系的新的有价值信息，并为抗惊厥活性的基本分子要求提供了重要见解。
